Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Jan 27, 2022; 13(1): 15-34
Published online Jan 27, 2022. doi: 10.4331/wjbc.v13.i1.15
Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats
Christian Carpéné, Luc Marti, Nathalie Morin
Christian Carpéné, Luc Marti, Nathalie Morin, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, Toulouse 31342, France
Nathalie Morin, Faculté de Pharmacie de Paris, Paris University, Paris 75270, France
Author contributions: Carpéné C designed the studies, performed hexose uptake assays and literature review, and wrote the manuscript; Marti L performed binding studies, rat experiments, and data analysis, and contributed to the literature review; Morin N performed immunoblots and data analysis, and revised the manuscript.
Supported by Recurrent Grants from Institut National de la Santé et de la Recherche Médicale to the INSERM U1048.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France.
Institutional animal care and use committee statement: Rats were housed and manipulated according to the INSERM guidelines and European Directive 2010/63/UE by competent and expert technicians or researchers in animal care facilities with agreements number A 31 555 04 to C 31 555 011. The experimental protocol was approved by the local ethical committee CEEA nb122.
Conflict-of-interest statement: All authors declare no competing financial interests for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Christian Carpéné, PhD, Senior Researcher, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, CHU Rangueil, Bat. L4, BP 84225, Toulouse 31342, France. christian.carpene@inserm.fr
Received: March 26, 2021
Peer-review started: March 26, 2021
First decision: July 8, 2021
Revised: July 9, 2021
Accepted: January 13, 2022
Article in press: January 13, 2022
Published online: January 27, 2022
Processing time: 301 Days and 14.5 Hours
ARTICLE HIGHLIGHTS
Research background

The genetically obese Zucker rat is hyperphagic and accumulates the excess of calorie intake in the form of lipids in spite of the insulin-resistant state of its adipocytes.

Research motivation

To investigate what biological events or natural biochemical processes drive the glucose utilization in fat cells of obese Zucker rats, which are not fully responsive to the lipogenic action of insulin.

Research objectives

Hydrogen peroxide is a biological chemical that can mimic several insulin actions on adipocytes, such as stimulating glucose entry and lipogenesis, and inhibiting lipolysis. Since it is a product of various enzymes in adipocytes, we focused our objective in searching whether the expression activity and biological effect of two types of them, namely, the monoamine oxidase (MAO) and semicarbazide sensitive amine oxidase (SSAO), abundant in adipocytes, were modified in obesity states.

Research methods

Experimental methods included Zucker rat husbandry, with obese and lean littermates (the former bearing homozygotous recessive mutation of fa/fa gene), preparations of freshly isolated adipocytes, functional exploration of hexose transport using uptake assays with appropriate pharmacological agents, and determination of lipogenic activity, immunobloting, measurement of amine oxidase activities, and saturation binding analyses.

Research results

There is a good relationship between the increased binding capacity of tritiated-idazoxan and tritiated-(2-benzofuranyl)-2-imidazoline to imidazoline binding sites and the increased MAO-dependent tyramine oxidation in adipose tissue of obese rats. Stimulation of MAO or SSAO by their substrates in the presence of vanadate reproduced approximately two-thirds of the insulin stimulation of glucose uptake in fat cells. However, this insulin-like effect decreased as the insulin responsiveness of adipocytes decreased with obesity.

Research conclusions

It cannot be stated whether the changes in MAO and SSAO expression are a cause or a consequence of the altered glucose handling in the fat cells of obese Zucker rats. At least, the increased tyramine oxidation is found in adipose tissues of the obese rats, not in the liver or in skeletal muscles, and can be associated with the dysregulation of the catecholaminergic system and of the energy balance found in that animal model of genetic obesity.

Research perspectives

The increase of MAO activity in adipose tissue from obese rats has never been reported, at least to our knowledge. Among the limitations of our first description of an increased MAO activity in the adipose tissue of this animal model of obesity, is that we did not decipher the mechanisms supporting such up-regulation, and that it remains unclear whether elevated MAO is a cause or a consequence of the dysmetabolic profile of the Zucker obese rats. This issue deserves further investigations.